The rationale of BACE inhibition is that it represents an upstream interference with the amyloid cascade and reduces cleavage of APP that leads to Aβ production. In April 2012, Phase I data on inhibitor MK-8931 was presented. This drug reduced Aβ CSF levels up to 92% and was well tolerated by patients [26]. In March 2013, data was added from a 1 week trial in 32 mild to moderate AD patients, showing CSF Aβ levels decreased up to 84% . In 2012, Merck launched the EPOCH trial, an 18-month Phase II/III trial comparing 12, 40, or 60 mg/day of MK-8931 given as once-daily tablets to placebo in patients with mild to moderate AD. The trial includes conventional cognitive and functional primary outcomes, as well as sub-studies for biomarker outcomes indicating change in brain amyloid and CSF tau levels, as well as change in brain volume. Further, in 2013, Merck began the APECS trial in 1,500 participants with prodromal AD. These patients have measureable cognitive deficits and a positive PET scan with the newly FDA-approved amyloid tracer flutemetamol, but are not functionally impaired. APECS will compare the 12- and 40-mg once-daily dose to placebo over 24 months.